HIV-1-specific CTL in the genital and gut-associated mucosa is hypothesized to play an important role in controlling dissemination of HIV infection from mucosal tissues to the periphery and may be able to be induced by vaccination. To investigate these possibilities, three specific aims are proposed: To identify viral and host factors associated with the induction and maintenance of mucosal CTL in primary and clinically stable HIV-1 infection; to determine whether mucosal CTL can prevent dissemination of HIV-1 in repeatedly exposed but uninfected persons, and to determine if HIV-1 specific CTL can be induced in the genital tract and mucosa through vaccines administered mucosally. Evaluation of CTL activity will include determination of precursor (p)CTL frequency, epitope specificities, and recognition of autologous HIV-1 strains. Correlations between HIV-1 levels and CTL activity in the peripheral blood and mucosa will be performed in patients with primary infections and on anti-viral therapy.